Localization of CD4+ T cell epitope hotspots to exposed strands of HIV envelope glycoprotein suggests structural influences on antigen processing

摘要

The spectrum of immunogenic epitopes presented by theH2-IAb MHC class II molecule to CD4+ T cellshas been defined for two different (clade B and clade D) HIV envelope(gp140) glycoproteins. Hybridoma T cell lines were generated from miceimmunized by a sequential prime and boost regime with DNA, recombinantvaccinia viruses, and protein. The epitopes recognized by reactive Tcell hybridomas then were characterized with overlapping peptidessynthesized to span the entire gp140 sequence. Evidence of clonalityalso was assessed with antibodies to T cell receptor Vα and Vβchains. A total of 80 unique clonotypes were characterized from sixindividual mice. Immunogenic peptides were identified within only fourregions of the HIV envelope. These epitope hotspots comprisedrelatively short sequences (≈20–80 aa in length) that were generallybordered by regions of heavy glycosylation. Analysis in the context ofthe gp120 crystal structure showed a pattern of uniform distribution toexposed, nonhelical strands of the protein. A likely explanation isthat the physical location of the peptide within the native proteinleads to differential antigen processing and consequent epitopeselection.